PET ANALYSIS OF [C-11] FLUMAZENIL BINDING TO BENZODIAZEPINE RECEPTORSIN CHRONIC ALCOHOL-DEPENDENT MEN AND HEALTHY CONTROLS

Benzodiazepine (BZ) receptor binding in the brain was determined in fi ve chronic alcohol-dependent men and in five healthy male control subj ects using [C-11]flumazenil (Ro 15-1788) and positron emission tomogra phy (PET). Magnetic resonance imaging was used to evaluate brain anato my and pathology, and to define regions of interest in the brain. [C-1 1]Flumazenil binding was quantified by applying a saturation procedure with two PET experiments, the first with high (400-3400 Ci/mmol) and the second with low (almost-equal-to 1 Ci/mmol) specific radioactivity . Radioactivity in the pons was taken as an estimate of free and nonsp ecifically bound radioligand. Equilibrium was defined to prevail when the derivative of specific binding (dC(b)(t)/dt) was equal to zero. Th e values were used in a Scatchard analysis for determination of the ma ximum density of binding sites (B(max)) and the equilibrium binding co nstant (K(d)). The mean values of B(max) and K(d) were about the same in the two groups, but the B(max) variance for the alcoholics was sign ificantly greater for all regions of interest as compared with the hea lthy volunteers. The results may indicate that chronic alcohol consump tion has multiple effects on the BZ receptor complex.